THE ROLE OF OXIDATIVE STRESS IN NEURODEGENERATIVE DISEASES: MECHANISMS AND THERAPEUTIC IMPLICATIONS

Abstract

Objective: The involvement of oxidative stress in cell death mechanisms during neurodegenerative diseases, with a focus on Alzheimer's disease, idiopathic Parkinson's disease, and amyotrophic lateral sclerosis (ALS), along with the exploration of antioxidant therapeutic strategies.

Background: Oxidative stress is implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, ALS, and Parkinson's disease. These diseases are characterized by selective neuronal loss and the accumulation of intracytoplasmic materials, suggesting common physiopathological mechanisms. The increase in disease frequency with age, existence of sporadic and familial forms, and possible co-occurrence of these conditions in certain populations further support the role of oxidative stress.

Methods: This review synthesizes literature on the involvement of oxidative stress in Alzheimer's disease, ALS, and Parkinson's disease, highlighting abnormal markers of oxidative stress in these conditions. The review also discusses antioxidant therapeutic strategies and their efficacy in clinical trials.

Results: In Alzheimer's disease, oxidative stress is associated with beta-amyloid protein, inflammation, and neuronal calcium metabolism disturbances. Antioxidants such as vitamin E, selegiline, vitamin C, Ginkgo Biloba extract, and non-steroidal anti-inflammatory drugs show promising effects. In ALS, hypotheses include excitotoxicity and genetic mutations affecting superoxide dismutase. Antioxidant trials have shown limited efficacy, with vitamin E in combination with riluzole being the most promising. In Parkinson's disease, oxidative stress contributes to dopaminergic neuron death, with evidence implicating iron accumulation and respiratory chain dysfunction. Selegiline demonstrates efficacy, while vitamin E shows mixed results.

Conclusion: Oxidative stress plays a significant role in neurodegenerative diseases, contributing to cell death mechanisms. Antioxidant therapies have been explored, showing variable efficacy across different conditions. Further research is needed to elucidate the precise mechanisms of oxidative stress and optimize therapeutic interventions for neurodegenerative diseases.